Biomedical subjects

Lee Yong Lim

Publications and source records attributed to Lee Yong Lim.

7 recordsLinked to original sources

PubMed2004

Flexible chitin films: structural studies.

Chitin gels were transformed into thin, flexible chitin films with minimal dimensional shrinkage and maximum flexibility and thickness in the range of 25-80 microm by a cold-press process. Solvent residue was removed by heating the films at 50 degrees C for 12 h, followed by rinsing in 95% ethanol. The crystallinity and mechanical properties of the flexible chitin films were found to be a function of the amount of shrinkage from the gel to the final film that was obtained. For 28-microm thick films with 30% shrinkage, transparency of up to 90% was found. X-ray diffractometry (XRD) showed that the number of diffraction peaks appearing at 2theta;=23 degrees and 2theta;=27 degrees became increasingly sharper with shrinkage. Topographical information obtained from scanning electron microscopy (SEM) and atomic force microscopy (AFM) attributed the structural morphology of the films to the formation of sub-microscopic micelles. Scanning transmission electron microscopy (STEM) showed that shrinkage resulted in coarser microstructure, affecting tensile properties, where the ductility and toughness were proportional to the amount of shrinkage. These flexible chitin films have potential as wound dressing materials.

Bandages↗

PubMed2004

Hydroxyapatite-chitin materials as potential tissue engineered bone substitutes.

Hydroxyapatite (HA) in 25%, 50% and 75% w/w fractions was incorporated into chitin solutions and processed into air- and freeze-dried materials. These HA-chitin materials were exposed to cell cultures and implanted into the intramusculature of a rat model. The HA-chitin materials were found to be non-cytotoxic and degraded in vivo. The presence of the HA filler enhanced calcification as well as accelerated degradation of the chitin matrix. The freeze-dried HA-chitin matrixes were selected for further cell seeding experiments because of their porous nature. Mesenchymal stem cells harvested from NZW rabbits were induced into osteoblasts in vitro using dexamethasone. These osteoblasts were cultured for 1 week, statically loaded onto the porous HA-chitin matrixes and implanted into bone defects of the rabbit femur for 2 months. Histology of explants showed bone regeneration with biodegradation of the HA-chitin matrix. Similarly, green fluorescence protein (GFP) transfected MSC-induced osteoblasts were also loaded onto porous HA-chitin matrixes and implanted into the rabbit femur. The results from GFP-transfected MSCs showed that loaded MSCs-induced osteoblasts did not only proliferate but also recruited surrounding tissue to grow in. This study demonstrates the potential of HA-chitin matrixes as a good substrate candidate for tissue engineered bone substitute.

Animals↗

PubMed2004

Herbal modulation of P-glycoprotein.

P-glycoprotein (Pgp) is a 170 kDa phosphorylated glycoprotein encoded by human MDR1 gene. It is responsible for the systemic disposition of numerous structurally and pharmacologically unrelated lipophilic and amphipathic drugs, carcinogens, toxins, and other xenobiotics in many organs, such as the intestine, liver, kidney, and brain. Like cytochrome P450s (CYP3A4), Pgp is vulnerable to inhibition, activation, or induction by herbal constituents. This was demonstrated by using an ATPase assay, purified Pgp protein or intact Pgp-expressing cells, and proper probe substrates and inhibitors. Curcumin, ginsenosides, piperine, some catechins from green tea, and silymarin from milk thistle were found to be inhibitors of Pgp, while some catechins from green tea increased Pgp-mediated drug transport by heterotropic allosteric mechanism, and St. John's wort induced the intestinal expression of Pgp in vitro and in vivo. Some components (e.g., bergamottin and quercetin) from grapefruit juice were reported to modulate Pgp activity. Many of these herbal constituents, in particular flavonoids, were reported to modulate Pgp by directly interacting with the vicinal ATP-binding site, the steroid-binding site, or the substrate-binding site. Some herbal constituents (e.g., hyperforin and kava) were shown to activate pregnane X receptor, an orphan nuclear receptor acting as a key regulator of MDR1 and many other genes. The inhibition of Pgp by herbal constituents may provide a novel approach for reversing multidrug resistance in tumor cells, whereas the stimulation of Pgp expression or activity has implication for chemoprotective enhancement by herbal medicines. Certain natural flavonols (e.g., kaempferol, quercetin, and galangin) are potent stimulators of the Pgp-mediated efflux of 7,12-dimethylbenz(a)-anthracene (a carcinogen). The modulation of Pgp activity and expression by these herb constituents may result in altered absorption and bioavailability of drugs that are Pgp substrates. This is exemplified by increased oral bioavailability of phenytoin and rifampin by piperine and decreased bioavailability of indinavir, tacrolimus, cyclosporine, digoxin, and fexofenadine by coadministered St. John's wort. However, many of these drugs are also substrates of CYP3A4. Thus, the modulation of intestinal Pgp and CYP3A4 represents an important mechanism for many clinically important herb-drug interactions. Further studies are needed to explore the relative role of Pgp and CYP3A4 modulation by herbs and the mechanism for the interplay of these two important proteins in herb-drug interactions.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2004

Therapeutic drugs that behave as mechanism-based inhibitors of cytochrome P450 3A4.

Cytochrome P450 (CYP) 3A4 is not only the most abundant isoform in human liver but also metabolizes approximately 60% of the therapeutic drugs. This feature renders CYP3A4 highly susceptible to both reversible and irreversible (mechanism-based) inhibition. The latter is characterized by NADPH-, time- and concentration-dependent enzyme inactivation, occurring when some drugs are converted by CYPs to reactive metabolites. Mechanism-based inactivation of CYP3A4 by drugs can be due to the chemical modification of the heme, the protein, or both as a result of covalent binding of modified heme to the protein. The clinical pharmacokinetic effect of a CYP3A4 inactivator is a function of its KI, kinact and partition ratio and the synthesis rate of new or replacement enzyme. Predicting drug-drug interactions involving CYP3A4 inactivation is possible when proper pharmacokinetic principles are followed. However, the prediction may become difficult, since the clinical outcomes due to CYP3A4 inactivation depend on many factors associated with the enzyme, drugs and the patients. A number of clinically important drugs have been identified to be mechanism-based CYP3A4 inhibitors. These include antibiotics (e.g. erythromycin and isoniazid), anticancer drugs (e.g. tamoxifen), antidepressants (e.g. fluoxetine and midazolam), anti-HIV agents (e.g. ritonavir and delavirdine), antihypertensives (e.g. dihydralazine and verapamil), steroids and their receptor modulators (e.g. gestodene and raloxifene), and some herbal constituents (e.g. bergamottin and glabridin). Compared to reversible inhibition, mechanism-based inhibitors of CYP3A4 more frequently cause unfavorable drug-drug interactions, as the inactivated CYP3A4 has to be replaced by newly synthesized CYP3A4 protein. Most CYP3A4 inactivators are also PgP substrates/inhibitors, confounding the in vitro-in vivo extrapolation. Clinicians should have good knowledge on these CYP3A4 inactivators and avoid their combination use.

Animals↗

PubMed2003

Flexible chitin films as potential wound-dressing materials: wound model studies.

Chitin films possessing increased flexibility, softness, transparency, and conformability have been prepared. These attributes enable the potential application of chitin films as occlusive, semipermeable film wound dressings similar to commercial products such as Opsite trade mark. The chitin films are generally nonabsorbent, exhibiting a total weight gain of only up to 120-160% in physiological fluid. Dry chitin films transpire water vapor at a rate of about 600 g/m(2)/24 h, similar to commercial polyurethane-based film dressings, but rises to 2400 g/m(2)/24 h, when wet, which is higher than the water vapor transmission rate of intact skin. The chitin films are nontoxic to human skin fibroblasts, maintaining 70-80% cell viability. Wound studies using a rat model showed no signs of allergenicity or the high inflammatory response associated with biodegradable biomaterials. The chitin films displayed accelerated wound-healing properties. Based on histological examination, wound sites dressed with the chitin films stabilized and healed faster, and appeared stronger than those dressed with Opsite trade mark and gauze dressings after 7 days of healing.

Animals↗

PubMed2003

Implantable applications of chitin and chitosan.

Chitin, extracted primarily from shellfish sources, is a unique biopolymer based on the N-acetyl-glucosamine monomer. More than 40 years have lapsed since this biopolymer had aroused the interest of the scientific community around the world for its potential biomedical applications. Chitin, together with its variants, especially its deacetylated counterpart chitosan, has been shown to be useful as a wound dressing material, drug delivery vehicle and increasingly a candidate for tissue engineering. The promise for this biomaterial is vast and will continue to increase as the chemistry to extend its capabilities and new biomedical applications are investigated. It is interesting to note that a majority of this work has come from Asia. Japan has been the undisputed leader, but other Asian nations, namely Korea, Singapore, Taiwan and Thailand have also made notable contributions. More recently, China has joined the club to become an increasingly major research source for chitin and chitosan in Asia. This review surveys select works of key groups in Asia developing chitin and chitosan materials for implantable biomedical applications.

Animals↗

PubMed2002

Chitosan-alginate PEC membrane as a wound dressing: Assessment of incisional wound healing.

Flexible, thin, transparent, novel chitosan-alginate polyelectrolyte complex (PEC) membranes, cast from aqueous suspensions of chitosan-alginate coacervates with CaCl(2), were evaluated as potential wound-dressing materials. MTT and NR assays suggested that the chitosan-alginate PEC membranes and their aqueous extracts were nontoxic towards mouse and human fibroblast cells. Cell growth was also not hindered by co-incubation with the membranes. Compared to conventional gauze dressing, the PEC membranes caused an accelerated healing of incision wounds in a rat model. Wounds closed at 14 days postoperatively, and histological observations showed mature epidermal architecture with keratinized surface of normal thickness and a subsided inflammation in the dermis. This was followed by an excellent remodeling phase with organized thicker collagen bundles and mature fibroblasts at 21 days postoperative. Control wounds continued to show signs of an active inflammatory phase under scab on Day 21. Closure rate and appearance of PEC membrane-treated wounds were comparable with Opsite(R)-treated wounds. On the basis of its biocompatibility and wound-healing efficacy, the chitosan-alginate PEC membrane can be considered for wound-dressing applications.

Alginates↗